The present invention relates to novel zinc oxide powder blends, their production and use and particularly, although not exclusively their use in cosmetics compositions. The invention includes methods of producing the novel zinc oxide powder blends, the zinc oxide powder blends produced, and end-product formulations incorporating the zinc oxide powder blends. Without limitation the invention furthermore includes cosmetic, pharmaceutical and sunscreen formulations, as well as cosmetic and sunscreen formulations all having UV-protective properties attributable to the incorporated zinc oxide blends. The ultraviolet (“UV” herein) region of the electromagnetic spectrum comprises three wavebands, designated UVA from 320 to 400 nm, UVB from 290 to 320 nm and UVC from 200 to 290 nm. The UVA bank can be further divided into UVAI from 320 to 340 nm and UVAII from 340 to 400 nm. The visible portion of the spectrum is generally from about 400 to about 700 nm. Natural sunlight is a potent source of UV radiation. UV radiation may compose about 10 percent of the solar radiation reaching the earth's surface and is well recognized as the cause of serious biological damage to humans and other animals.
Awareness of the risks and prevalence of UV-induced skin cancer and consciousness of the damaging cosmetic effects of ultraviolet radiation have fostered recognition in recent years of the desirability of avoiding or controlling the physiological damage wrought by harmful ultraviolet radiation, especially solar ultraviolet. UVC radiation is generally not problematic as little if any penetrates the atmosphere, but may be hazardous if artificial sources such as germicidal lamps or high or low pressure mercury arc lamps are employed.
In contrast to the UVC waveband which is filtered out, both UVA and UVB radiation reach the earth's surface from the sun and may be harmful. Longer wavelength ultraviolet rays in the UVA region, adjacent the visible spectrum, which reportedly constitute 99% of the UV energy reaching the earth's surface, are considered to be the primary cause of tanning but to cause little burning. However, in the longer term UVA rays are also believed responsible for skin aging, causing blotching, freckling, wrinkling and comparable problems. Ultraviolet radiation in the shorter wavelength UVB region of from 290 to 320 nm, though comprising only about 1% of the UV energy is considered more significant in causing burning. Accordingly, protection against UVB radiation has traditionally been a primary target of sunscreen formulation. More recently, there has been a recognition of the desirability of also protecting against UVA radiation to reduce long term skin deterioration.
More seriously, both the UVA and UVB wavebands may be implicated in skin cancers including dangerous melanomas. Skin cancer is by far the most prevalent of all cancers and the incidence in the US is increasing rapidly. for these and other reasons, consistent use of a topical sunscreen is now strongly recommended and is widespread. In light of this need, the art contains many proposals for sunscreen agents and compositions intended to provide protection from damaging ultraviolet radiation.
Many and diverse UV-protective agents suitable for topical application in creams, sprays, lotions and the like is known and has been used in sunscreens. However, most such agents are organic chemicals that are prone to photodegradation and may cross-react with other components of desirable topical formulations. Furthermore, being absorbable into the skin, organic sunscreens may irritate the skin or cause other dermatological or allergenic problems. The art also contains proposals for broad spectrum UV protection.
For example, Deckner U.S. Pat. No. 5,783,174 describes sunscreen compositions intended to provide broad protection in both the UVA and UVB regions which compositions combine a UVA-absorbing dibenzoylmethane sunscreen with a UVB-absorbing benzylidene camphor sunscreen. This composition is intended to avoid problems of photochemical instability attributable, according to Deckner, to photoinduced interaction between dibenzoylmethane and the widely used UVB absorber octylmethoxy cinnamate.
A more recent demand for both higher SPF (“sun protection factor”) values and for broad-spectrum protection, has led manufacturers to combine several different organic chemical ingredients, aggravating potential problems of photo-induced cross reactivity. To overcome this problem, Lapidot, et al. describe in U.S. Pat. No. 6,436,375 a method for microencapsulating at least one of two or more active sunscreen ingredients which are photo-unstable when formulated together. The active ingredients can be selected for UVA and UVB activity and can be encapsulated in separate sol-gel microcapsules. A drawback of Lapidot et al.'s proposal is that even if problems of cross-reactivity and photodegradation can be overcome, which may or may not be the case, Lapidot et al.'s method still requires use of active organic sunscreen agents which may be harmful or irritating when absorbed. Furthermore, use of sol-gel microcapsules adds complexity and expense and may be undesirable in some topical formulations. Such microcapsules may also raise issues of dispersibility and compatibility with other ingredients of end product formulations.
There is accordingly a need for a UV-protective agent having broad spectrum activity against harmful solar radiation and which does not depend upon organic chemicals. In light of the problems with organic materials, the suitability of inorganic materials may be considered. Several commercially useful inorganic UV-protective agents are known, notably titanium dioxide, zinc oxide and iron oxide. Iron oxides, however are usually colored or black and therefore have rather limited use in sunscreen applications. Also, they may not be approved for use as sunscreens by regulatory authorities such as the US FDA.
Thus, considerable difficulties face a formulator or other worker seeking broad spectrum UV-protective agents that will be satisfactory for widespread commercial use in a full range of topical commercial products.
Elsom et al. (WO 90/11067) provide single-species metal oxide sunscreen compositions. Specifically provided are sunscreen compositions containing blends of titanium dioxide powders having a particle size of 1-100 nm.
Likewise, Cowie et al. U.S. Pat. No. 4,927,464 also provides single-species titanium dioxide compositions for absorbing UV radiation. Cowie et al. use acicular titanium dioxide wherein the length of the longest dimension is 10-150 nm and the particles are coated with a mixture of alumina and silica.
Iwaya U.S. Pat. No. 5,032,090 suggests use of a combination of titanium dioxide and zinc oxide in anti-suntan cosmetic compositions to block ultraviolet rays in both the UVB and UVA regions. One drawback of this approach is that titanium dioxide may undesirably whiten or blue the skin in some formulations. Also the use of multiple metal oxides having significant reactivity in many sunscreen systems may complicate the issues a formulator of compositions for human topical application must address. Furthermore, although titanium dioxide is approved by regulatory agencies for many UV-protective applications, it is not approved for use in combination with avobenzone, a popular organic sunscreen agent. In addition, titanium is not naturally present in human and other organisms, and may therefore be an undesired ingredient for some prospective users.
Iwaya U.S. Pat. No. 5,032,090 suggests use of a combination of titanium dioxide and zinc oxide with a primary particle size great than 70 nm to 300 run in anti-suntan cosmetic compositions to block ultraviolet rays in both the UVB and UVA regions. The primary particle size of the zinc oxide claimed is too large to be effective in UVB.
Other formulations of the prior art use single-species zinc oxide compositions for UV absorption. For example, Kobayashi Kose Co. JP 60-231607 provides anti-suntan cosmetics containing 10-30% zinc oxide having a particle diameter of <100 nm.
Mitchell et al. U.S. Pat. No. 5,587,148 discloses sunscreen products intended to absorb both UVA and UVB radiation while providing a clear appearance on the skin. One embodiment of Mitchell et al.'s disclosure employs micronized particles of zinc oxide having a size up to about 0.2 μm and having what are purportedly reduced levels of toxic heavy metals, which are formulated with a liquid carrier into a colorless emulsion. According to Mitchell et al., this formulation “is capable of absorbing a substantial quantity, if not all, of the UV radiation to which the user is exposed.” (Column 7, lines 15-17.) However, the Mitchell et al. specification provides little, if any, support for this conclusion. Other distinct embodiments proposed by Mitchell et al. include: use of large crystals of zinc oxide, measuring between about 1-100 microns in diameter; and use of transparent plastic spheres measuring between about 0.01-100 microns in diameter which incorporate a UV-absorbing additive.
Cole et al. U.S. Pat. No. 5,340,567 provides sunscreen products intended for UV absorbance. Cole et al. provide mixed metal oxide compositions containing titanium dioxide having a particle size of less than about 35 nm and zinc oxide having a particle size of less than about 50 nm. The metal oxide particles used by Cole et al. are each of a single substantially uniform size.
A disclosure by inventors herein Yun Shao and David Schlossman, “Effect of Particle Size on Performance of Physical Sunscreen formulas” PCIA conference, Shanghai, China R. P. (1999) (“Shao et al. 1999” hereinafter) and available, at the date of this application, describes some of the effects of size, surface treatment, dispersion vehicle, dispersant and other factors on the UV-protective performance of inorganic sunscreens, notably titanium dioxide and zinc oxide. Shao et al. 1999 emphasize the importance of studying size reduction and the relationship between particle size and performance.
Shao et al. 1999 describe use of dispersions, or “pre-dispersions” of titanium dioxide and zinc oxide, intended for formulation with other ingredients to provide useful end product. Shao et al. 1999 concluded at that time that a high loading of solids in the dispersion were important to size reduction and that other factors should also be considered, including pigment selection, surface treatment, vehicle and dispersant. Titanium dioxide is described as providing excellent protection against UVB along with effective UVA protection at a larger size where scattering may contribute significantly. However, such larger sizes may sacrifice some degree of SPF and transparency.
The protection afforded by zinc oxide is considered by Shao et al. 1999 to vary inversely with particle size. Also, zinc oxide is described as providing efficient UVA protection, often with a low SPF. One difficulty these findings present to the worker seeking to provide a broad-spectrum inorganic UV-protective agent suitable for topical application, is that desired sizes of titanium dioxide particles may cause whitening on the skin, as may be understood from FIG. 5 of Shao 1999. (Nor does Shao et al. 1999 describe an adequate zinc oxide formulation.
Another disclosure of inventors, Yun Shao and David Schlossman herein, namely Discovering an Optimum Micropigment for High UV Shielding and Low Skin Whitening, 23rd IFSCC Congress Orlando 2004 (“Shao et al. 2004” hereinafter) describes studies on the UV attenuation of dispersions of titanium dioxide having a primary particle size (“PPS”) as small as 15 nm and of zinc oxide as small as 20 nm which studies include studies of their in vivo SPF efficacy. Shao et al. 2004 conclude that size reduction of titanium dioxide and zinc oxide can remarkably improve the appearance of a sunscreen lotion and can improve the SPF in many cases. However, according to Shao et al. 2004, if the size of the titanium dioxide particles is too small, the energy absorption may shift to UVC wavelengths, weakening the attenuation in the UVA and UVB wavebands. Shao et al. 2004 conclude that zinc oxide could provide an effective SPF at (secondary) particle sizes under 130 nm, but “at the cost of UVA protection”.
In this specification, “primary particle size” may be understood to reference an average or mean particle size of the metal oxide as dry powder while “particle size” sometimes referenced herein as “secondary particle size” for greater clarity, can be understood to reference the average mean particle size as it is determined in a dispersion of the metal oxide powder in a liquid.
As may be understood from Shao et al. 2004, secondary particle size may often be more important for ultraviolet protection than is the primary particle size, but the primary particle size of the dry powder is often, but not always, a principal factor in determining the secondary particle size in a liquid dispersion. Some of the data described in Shao et al. 2004 shows that secondary size does not always correlate with primary size. The secondary particle size will usually be substantially greater than the primary particle size, possibly as much as five times greater or even more.
In vivo studies reported in boxes 7-9 of Shao et al. 2004 describe several properties of sunscreens employing the described titanium dioxide and zinc oxide dispersions, including the SPF, the SPF per % of active ingredient and, in box 8, the PFA. “PFA” is a measure of the protection afforded against UVA. Desirable values for PFA may be in the range of from about 4 to about 8. Referring to box 8, which addresses the UV protection of zinc oxide dispersions, no PFAs are reported for the first three test samples, reading down Table 7, which are all described as having relatively smaller (secondary) particles sizes, “PS(nm)”, of 110 nm or 130 nm. The last three samples are described as having larger (secondary) particles sizes of 228 nm, or greater, and yield PFAs which are in the target range.
EIsom et al. (WO 90/11067) provide sunscreen compositions which comprise a blend of different particle sizes of titanium dioxide. Preferred compositions comprise 10 to 70% of titanium dioxide having a mean primary particle size of about 15 nm and at least one further grade of titanium dioxide having a mean primary particle size of between about 30 nm and about 50 nm. One drawback of this approach is that titanium dioxide may undesirably whiten or blue the skin in some formulations. The compositions are described as substantially transparent, however, because the refractive index of titanium dioxide is 2.6 they are likely to be too whitening when the objective is to obtain an SPF 25 with a UV balance of 4:1.
“Shao et al. 2004” is here described for the sake of completeness in elucidating the background of the present invention. However, it is to be understood that no admission is made regarding the availability of Shao et al. 2004 as a reference in the United States or any other state or region against the claims of the present application.
Thus notwithstanding the foregoing and other proposals in the art, there is a need for improved UV-protective compositions having properties satisfying the various cosmetic and prophylactic needs of the end user as well as the requirements of a cosmetic formulator who must provide appealing, functional products which can be provided to consumers in a satisfactory and aesthetic condition.
In an earlier filed P.C.T. Patent Application No. PCT/US2006/041417, filed Oct. 23, 2006, we describe a composition which provides an inorganic UV-protective composition which can provide broad-spectrum UV protection, while also being capable of being formulated into end products which have good transparency to visible light on the skin.
Generally, in accordance with the present invention, sunscreen ingredients for cosmetics, suntanning lotion, or the like in both powder and in liquid dispersion form are made from two different sunscreen materials. Each of these two different sunscreen materials is selected for its characteristic of addressing either the UVA or the UVB component of sunlight. In connection with this, it is noted that both of these components will attenuate UVA and UVB, but are, in the context of the multi-mode formulations of the present invention, more effective in addressing either the UVA or the UVB component.
A desirable additional object of the invention is to provide an inorganic UV-protective composition capable of being formulated into dispersions which are non-whitening or induce little whitening at high solids loadings. A still further useful object is to provide dispersions containing the inorganic UV-protective composition that avoid or induce little bluing on pigmented skin.
These and other objects can be achieved by one or more embodiments of the invention described herein.
In one aspect, the invention provides a zinc oxide powder composition for UV-protective use comprising a blend of:
a) an effective proportion of a first zinc oxide powder component having a first particle size selected for the first zinc oxide powder component to attenuate UVA; and
b) an effective proportion of a second zinc oxide powder component having a second particle size selected for the second zinc oxide powder component to attenuate UVB;
wherein the mean particle size of the first zinc oxide component is greater than the mean particle size of the second zinc oxide component.
The relative proportions of the first and second zinc oxide components can be adjusted, or selected, to provide a desired balance of UVA versus UVB protection. For example, the proportion by weight of the first component to the second component may be selected to be in the range of from about 1:2 to about 2:1. Some useful embodiments of the invention employ a proportion by weight of the first component to the second component in the range of from about 1:1.4 to about 1:1.
In another aspect, the invention provides a UV-protective composition comprising an effective amount of a first zinc oxide particulate component having a mean primary particle size in the range of from about 30 to about 200 nm and an effective amount of a second zinc oxide particulate component having a mean primary particle size in the range of from about 10 to about 30 nm. As indicated above, “primary particle size” references the size of the dry, untreated powder.
In a further aspect, the invention provides an UV-protective composition comprising a dispersion in a liquid vehicle of an effective amount of a first zinc oxide particulate component having a mean secondary particle size greater than about 180 nm and an effective amount of a second zinc oxide particulate component having a mean secondary particle size less than about 150 nm. As indicated above, the secondary particle size references the size of the particles in the dispersion. Particle sizes referenced herein are as determined by light scattering analysis, as described hereinafter unless otherwise indicated explicitly or by the context.
Suitable dispersions may employ hydrocarbon or other fluids or oils or silicone fluids as liquid vehicles, although aqueous vehicles may also be used. The dispersions are preferably solids-rich. Usefully, the solids-rich zinc oxide dispersions may employ effective, usually small, proportions of chemical dispersing agents, or dispersants, as is known to those skilled in the art. Also the zinc oxide particles may be coated to enhance their dispersibility, as is also known in the art.
Alternatively, the formulator may incorporate the zinc oxide powder blend, in powder form, with other suitable ingredients to prepare a final product. As a further alternative the zinc oxide powder components, rather than being pre-blended may be separately added.
The two zinc oxide components can be supplied for incorporation into the UV-protective product as a particulate or powder blend or may be separately added to one or more other ingredients to provide the UV-protective composition. Some process embodiments of the invention include steps of blending the two or more dry zinc oxide powder ingredients together and adding the blend to other ingredients. Pursuant to the invention it is believed that, in end product formulations, the first and larger zinc oxide component can provide useful UVA protection and the second and smaller zinc oxide component can provide useful UVB protection.
The first zinc oxide powder component can have a mean primary particle size in the range of from about 50 to about 200 nm to provide UVA protection. In one embodiment of the invention the primary particle size of the first zinc oxide component is in the range of from about 60 to about 100 nm.
The second zinc oxide powder component can have a mean primary particle size in the range of from about 10 to about 30 nm to provide UVB protection. In another embodiment of the invention the primary particle size of the second zinc oxide component is about 20 nm.
Our earlier composition contemplated embodiments employing combinations of the mean particle sizes of the first and second components, for example one tranche of zinc oxide particles having a mean size in the range of about 50 to about 200 nm with another tranche of zinc oxide particles having a mean size in the range of about 10 to about 30 nm, for particles of size of from about 60 to about 100 nm of the first component may be combined with particles of size of about 20 nm of the second component.